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PHLPP : a novel family of phosphatases that are critical regulators of iIntracellular signaling pathways

Abstract

A fundamental aim in cell signaling is to decipher how phosphorylation and dephosphorylation regulate cell fate. In order to achieve this goal the scientific community must have a complete understanding of the proteins involved in regulating cellular processes. To this end we have discovered a novel family of phosphatases referred to as PHLPP, (PH domain leucine-rich repeat protein phosphatase). These Ser/Thr specific phosphatases have emerged as important regulators of intracellular signaling pathways by acting as the brakes to lipid second messenger signaling. This thesis will focus on characterizing the novel phosphatase PHLPP2 and defining its role in regulation of the PI3K/Akt pathway. Second, it addresses whether these phosphatases are involved in the process of tumorigenesis. Lastly, it will examine the role of PHLPP in regulation of the related kinase, protein kinase C. In summary, this thesis is a first step in understanding the role of PHLPP in normal tissue homeostasis as well as pathophysiological states

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